Abstract
The aim of this study was to identify the hepatoprotective effects of reynosin, sesquiterpenes from the leaves of Laurus nobilis, against thioacetamide (TAA)-induced apoptosis in primary hepatocyte cultures and an in vivo mouse model. Rat hepatocytes were isolated and pretreated with 0.13, 0.64, or 3.22 μM reynosin and then exposed to 100 mM TAA. Reynosin treatment significantly inhibited TAA-induced apoptosis and hepatocellular DNA damage in primary rat hepatocytes. We observed an increase in levels of antiapoptotic Bcl-2, Bcl-XL mRNA and a decrease in levels of proapoptotic Bax mRNA following reynosin treatment of hepatocytes. Apoptosis in BALB/c mice was induced with intra-peritoneal injection of 200 mg/kg TAA for 2 weeks every other day. Then reynosin (5 mg/kg) and TAA were intragastrically given for 3 weeks every other day. Aspartate aminotransferase and alanine aminotransferase levels in the blood of mice were decreased in the reynosin administration group. Bcl-2 and Bcl-XL mRNA levels were increased, and the Bax mRNA level was decreased in reynosin-treated mice. Thus, reynosin inhibited TAA-induced apoptosis in primary hepatocytes and an in vivo mouse model.
Similar content being viewed by others
References
Caballero, M.E., J. Berlanga, D. Ramirez, P. Lopez-Saura, R. Gozalez, D.N. Floyd, T. Marchbank, and R.J. Playford. 2001. Epidermal growth factor reduces multiorgan failure induced by thioacetamide. Gut 48: 34.
Canbay, A., S. Friedman, and G.J. Gores. 2004. Apoptosis: The nexus of liver injury and fibrosis. Hepatology 39: 273.
Chen, L.H., C.Y. Hsu, and C.F. Weng. 2006. Involvement of P53 and Bax/Bad triggering apoptosis in thioacetamide-induced hepatic epithelial cells. World Journal of Gastroenterology 12: 5175.
Choi, J.Y., E.H. Choi, H.W. Jung, J.S. Oh, W.H. Lee, J.G. Lee, J.K. Son, Y. Kim, and S.H. Lee. 2008. Melanogenesis inhibitory compounds from saussureae radix. Archives of Pharmacy Research 31: 294.
Dai, K., J.Y. Qi, and D.Y. Tian. 2005. Leptin administration exacerbates thioacetamide-induced liver fibrosis in mice. World Journal of Gastroenterology 11: 4822.
De Marino, S., N. Borbone, F. Zollo, A. Ianaro, P. Di Meglio, and M. Iorizzi. 2005. New sesquiterpene lactones from Laurus nobilis leaves as inhibitors of nitric oxide production. Planta Medica 71: 706.
Dua, P., and R.P. Gude. 2006. Antiproliferative and antiproteolytic activity of pentoxifylline in cultures of B16F10 melanoma cells. Cancer Chemotherapy and Pharmacology 58: 195.
Dunschede, F., K. Erbes, A. Kircher, S. Westermann, J. Seifert, A. Schad, K. Oliver, A.K. Kiemer, and J. Theoddor. 2006. Reduction of ischemia reperfusion injury after liver resection and hepatic inflow occlusion by alpha-lipoic acid in humans. World Journal of Gastroenterology 12: 6812.
Franchini, C., F. Fontana, M. Minuzzo, F. Babbio, and E. Privitera. 2006. Apoptosis promoted by up-regulation of TFPT (TCF3 fusion partner) appears p53 independent, cell type restricted and cell density influenced. Apoptosis 11: 2217.
Faouzi, S., B.E. Burckhardt, J.C. Hanson, C.B. Campe, L.W. Schrum, R.A. Rippe, and J.J. Maher. 2001. Anti-Fas induces hepatic chemokines and promotes inflammation by an NF-kappa B-independent, caspase-3-dependent pathway. Journal of Biological Chemistry 276: 49077.
Goren, N., H.J. Woerdenbag, and C. Bozok-Johansson. 1996. Cytotoxic and antibacterial activities of sesquiterpene lactones isolated from Tanacetum praeteritum subsp. praeteritum. Planta Medica 62: 419.
Imao, M., M. Nagaki, M. Imose, and H. Moriwaki. 2006. Differential caspase-9-dependent signaling pathway between tumor necrosis factor receptor- and Fas-mediated hepatocyte apoptosis in mice. Liver International 26: 137.
Issa, H.H., Chang, S.M., Yang, Y.L., Chang, F.R. and Y.C. Wu. 2006. New sesquiterpene lactones from the aerial parts of Pseudoelephantopus spicatus. Chemical and Pharmaceutical Bulletin Tokyo. 54:1599.
Kanzler, S., and P.R. Galle. 2000. Apoptosis and the liver. Seminars in Cancer Biology 10: 173.
Lee, B.C., J.S. Yoo, K.Y. Baik, K.W. Kim, and K.S. Soh. 2005. Novel threadlike structures (Bonghan ducts) inside lymphatic vessels of rabbits visualized with a Janus Green B staining method. Anatomical Record B New Anatomist 286: 1.
Lopez-Anton, N., C. Hermann, R. Murillo, I. Merfort, G. Wanner, A.M. Vollmar, and V.M. Dirsch. 2007. Sesquiterpene lactones induce distinct forms of cell death that modulate human monocyte-derived macrophage responses. Apoptosis 12: 141.
Mantena, S.K., S.D. Sharma, and S.K. Katiyar. 2006. A natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells. Molecular Cancer Therapeutics 5: 296.
Masson, S., M. Scotte, S. Garnier, A. Francois, M. Hiron, P. Teniere, J. Fallu, J.P. Salier, and M. Daveau. 2000. Differential expression of apoptosis-associated genes post-hepatectomy in cirrhotic vs. normal rats. Apoptosis 5: 173.
Matsuda, H., H. Shimoda, K. Ninomiya, and M. Yoshikawa. 2002. Inhibitory mechanism of costunolide, a sesquiterpene lactone isolated from Laurus nobilis, on blood–ethanol elevation in rats: involvement of inhibition of gastric emptying and increase in gastric juice secretion. Alcohol and Alcoholism 37: 121.
Morio, L.A., H. Chiu, K.A. Sprowles, P. Zhou, D.E. Heck, M.K. Gordon, and D.L. Laskin. 2001. Distinct roles of tumor necrosis factor-alpha and nitric oxide in acute liver injury induced by carbon tetrachloride in mice. Toxicology and Applied Pharmacology 172: 44.
Nan, J.X., E.J. Park, Y.C. Kim, G. Ko, and D.H. Sohn. 2002. Scutellaria baicalensis inhibits liver fibrosis induced by bile duct ligation or carbon tetrachloride in rats. Journal of Pharmacy and Pharmacology 54: 555.
Ockner, R.K. 2001. Apoptosis and liver diseases: Recent concepts of mechanism and significance. Journal of Gastroenterology and Hepatology 16: 248.
Patel, T. 2000. Apoptosis in hepatic pathophysiology. Clinics in Liver Disease 4: 295.
Rust, C., and G.J. Gores. 2000. Apoptosis and liver disease. American Journal of Medicine 108: 567.
Sakulnarmrat, K., M. Fenech, P. Thomas, and I. Konczak. 2013. Cytoprotective and pro-apoptotic activities of native Australian herbs polyphenolic-rich extracts. Food Chemistry 136: 9–17.
Sukocheva, O.A., and D.O. Carpenter. 2006. Anti-apoptotic effects of 3,5,3′-tri-iodothyronine in mouse hepatocytes. Journal of Endocrinology 191: 447.
Yang, X.J., J. Liu, L.B. Ye, F. Yang, L. Ye, J.R. Gao, and Z.H. Wu. 2006. In vitro and in vivo protective effects of proteoglycan isolated from mycelia of Ganoderma lucidum on carbon tetrachloride-induced liver injury. World Journal of Gastroenterology 12: 1379.
Yoshikawa, M., H. Shimoda, T. Uemura, T. Morikawa, Y. Kawahara, and H. Matsuda. 2000. Alcohol absorption inhibitors from bay leaf (Laurus nobilis): Structure-requirements of sesquiterpenes for the activity. Bioorganic & Medicinal Chemistry 8: 2071.
Acknowledgments
This research was supported by the Basic Science Research Program of the National Research Foundation of Korea, funded by the Ministry of Education, Science and Technology (grant number 120120392).
Author information
Authors and Affiliations
Corresponding author
Additional information
Soohyun Lim and Sung-Jin Lee contributed equally to this study.
Rights and permissions
About this article
Cite this article
Lim, S., Lee, SJ., Nam, KW. et al. Hepatoprotective effects of reynosin against thioacetamide-induced apoptosis in primary hepatocytes and mouse liver. Arch. Pharm. Res. 36, 485–494 (2013). https://doi.org/10.1007/s12272-013-0039-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-013-0039-0